CN101069680B - Use of 2-hydroxyl-methyl benzenesulfonic acid in preparing medicine - Google Patents
Use of 2-hydroxyl-methyl benzenesulfonic acid in preparing medicine Download PDFInfo
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- CN101069680B CN101069680B CN2007101306527A CN200710130652A CN101069680B CN 101069680 B CN101069680 B CN 101069680B CN 2007101306527 A CN2007101306527 A CN 2007101306527A CN 200710130652 A CN200710130652 A CN 200710130652A CN 101069680 B CN101069680 B CN 101069680B
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- benzenesulfonic acid
- methyl benzenesulfonic
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Abstract
The present invention discloses 2-hydroxy-4-methylbenzenesulfonic acid preparation, its preparation method and application. It has the actions of coagulating protein, hemostasis and astringing wound, at the same time has the stronger action for killing pathogens (including Gram-negative bacterium, Gram-positive bacterium, fungi, mycoplasma, chlamydozoan and virus, etc.). It can be made into various different preparations for curing various diseases.
Description
Technical field
The present invention relates to the preparation of 2-hydroxy-4-methyl benzenesulfonic acid preparation and in medically application.
Background technology
Cresol class material still is being extensive use of so far as disinfection sanitizer.2-hydroxy-4-methyl benzenesulfonic acid is 6 sulfonated derivants of metacresol (R.D.Haworth, A.Lapworth, J.Chem.Soc. (London) 1924,1299), and its structural formula is as follows:
Molecular formula is C
7H
8O
4S, molecular weight are 188.According to existing reported literature, this chemical compound is used as dyestuff.
The inventor finds that unexpectedly 2-hydroxy-4-methyl benzenesulfonic acid not only has the activity of the pathogen killed, and has new pharmacological actions such as protein coagulation, astringing to arrest bleeding.
Summary of the invention
The invention provides a kind of pharmaceutical preparation of the 2-of containing hydroxy-4-methyl benzenesulfonic acid.Said preparation is to be prepared from by 2-hydroxy-4-methyl benzenesulfonic acid and the adjuvant that pharmaceutically allows.According to the present invention, said preparation is any pharmaceutically useful dosage form.Preferably suppository, gel, solution, ointment, vaginal tablet, vagina soft capsule, spray, foam or foam aerosol.
Preparation of the present invention is the 2-hydroxy-4-methyl benzenesulfonic acid and 0 by 0.1%-99.9% weight, and the adjuvant that pharmaceutically allows of 1%-99.9% weight is prepared from.
The present invention also comprises the preparation method of said medicine preparation, and this method comprises 2-hydroxy-4-methyl benzenesulfonic acid and the blended step of adjuvant that pharmaceutically allows.
The present invention also provides the medicinal usage of 2-hydroxy-4-methyl benzenesulfonic acid, and is particularly antibiotic in preparation, protein coagulation, the application in the astringency and hemostasis medicament.
Medicinal application of the present invention, particularly in gynecological, can be used for treating the hemostasis after pressure ulcer, cervical polyp excision or the cut sections for microscopic examination that cervical erosion, cervicitis, all kinds of vaginal infection, pruritus vulvae, use pessulum causes, condyloma acuminatum and quicken electric coagulation therapy after wound healing.Described application is the topical therapeutic that can be used for skin wound and pathological changes in surgery and department of dermatologry, the treatment that the antibacterial of skin surface, fungus etc. infect, operating hemostasis and be used for the treatment of condyloma acuminatum, described antibiotic be the inflammation that in the department of stomatology, can be used for treating oral mucosa and gums, oral ulcer and post tonsillectomic hemostasis.Described application is sterilization and the Personal hygiene cleaning that is used for apparatus, household, medicated clothing as disinfectant.
2-hydroxy-4-methyl benzenesulfonic acid has stronger acidity, local difficult the absorption, for this has carried out preferably dosage form, local topical preparation particularly is as suppository, gel, solution, ointment, vaginal tablet, vagina soft capsule, spray, foam, foam aerosol.
2-hydroxy-4-methyl benzenesulfonic acid suppository provided by the present invention can mix 2-hydroxy-4-methyl benzenesulfonic acid and the water-soluble base (as: Polyethylene Glycol etc.) or the fatty substrate (as: lanoline etc.) that pharmaceutically allow.This method may further comprise the steps: 2-hydroxy-4-methyl benzenesulfonic acid is water-soluble, with molten matrix mixing in advance, be poured in bolt shell or the bolt mould then, and cooling, molding gets final product.
2-hydroxy-4-methyl benzenesulfonic acid gel provided by the present invention can mix 2-hydroxy-4-methyl benzenesulfonic acid and the substrate (as: Polyethylene Glycol etc.) that pharmaceutically allows.This method may further comprise the steps: 2-hydroxy-4-methyl benzenesulfonic acid is water-soluble, then with molten matrix mixing in advance, stir cooling after, be poured in the gel tube and get final product.
2-hydroxy-4-methyl benzenesulfonic acid solution provided by the present invention can add 2-hydroxy-4-methyl benzenesulfonic acid the purified water dissolving and be diluted to the concentration of requirement, cannedly gets final product in bottle.
2-hydroxy-4-methyl benzenesulfonic acid vaginal tablet provided by the present invention can be with behind the 2-hydroxy-4-methyl benzenesulfonic acid crushing screening, with the adjuvant that pharmaceutically the allows mixing that sieves, makes soft material, granulate, and oven dry, behind the granulate, tabletting gets final product.
2-hydroxy-4-methyl benzenesulfonic acid foam provided by the present invention, can be with 2-hydroxy-4-methyl benzenesulfonic acid water-soluble after, add the adjuvant (foaming agent) that pharmaceutically allows, an amount of purified water of reuse is diluted to the concentration of requirement, is poured in the foamer to get final product.
With 2-hydroxy-4-methyl benzenesulfonic acid is crude drug, add the suitable adjuvant that pharmaceutically allows, can be made into series external preparations (as suppository, gel, solution, ointment, vaginal tablet, vagina soft capsule, spray, foam, foam aerosol etc.) and disinfectant, all dosage forms all can be used for gynecological, and gel wherein, solution, ointment can be used for surgery, department of dermatologry and the department of stomatology.Solution is after dilution, can be used for gynaecologic vaginal flushing, so that fast quick-recovery and keep the normal physiology pH value of human body, the generation of gynaecopathias such as prevention cervicitis, cervical erosion and vaginal infection, can also be used for Personal hygiene cleaning, the sterilization of apparatus, medicated clothing, household etc. as disinfectant.
The present invention finds 2 hydroxy-4-methyl benzenesulfonic acid medical usages first, and is made into pharmaceutical preparation, tests discovery through the present invention, pharmaceutical preparation of the present invention, curative effect is superior, few side effects, zest is little, and constant product quality is a kind of alternative good medicine.
The specific embodiment
Below in conjunction with specific embodiment, further lock is stated the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.
Embodiment 1
Get 2-hydroxy-4-methyl benzenesulfonic acid 9g, with the dissolving of 9g purified water.To gather 169g Macrogol 4000 and 116g cetomacrogol 1000 mixes a rearmounted 65-70 ℃ heating in water bath and makes fusing, stirring and evenly mixing, add 2-hydroxy-4-methyl benzenesulfonic acid aqueous solution then, after stirring, inject bolt shell or bolt mould, cooling promptly gets 2-hydroxy-4-methyl benzenesulfonic acid suppository (3g/ grain).
Embodiment 2
Get 2-hydroxy-4-methyl benzenesulfonic acid 9g, with the dissolving of 16g purified water.To gather the rearmounted 70 ℃ of heating in water bath of 395g PEG400 and 80g polyethylene glycol 6000 mixing and make fusing, stirring and evenly mixing, add 2-hydroxy-4-methyl benzenesulfonic acid aqueous solution then, after stirring and cooling off, pour in the gel tube, seal and promptly get 2-hydroxy-4-methyl benzenesulfonic acid gel (25g/ props up).
Embodiment 3
Get 2-hydroxy-4-methyl benzenesulfonic acid 36g, add and contain the 64g purified water, fully after the stirring and dissolving, divide in the 10ml bottle of packing into, promptly get 2-hydroxy-4-methyl benzenesulfonic acid solution (concentration is 36%).
Embodiment 4
Get 2-hydroxy-4-methyl benzenesulfonic acid 10g, add and contain the 990g purified water, fully after the stirring and dissolving, divide in the 100ml bottle of packing into, promptly get 2-hydroxy-4-methyl benzenesulfonic acid solution (concentration is 1%).
Embodiment 5
2-hydroxy-4-methyl benzenesulfonic acid 90g
Microcrystalline Cellulose 175g
Lactose 175g
Soluble starch 50g
Hydroxypropyl cellulose (LH-21) 50g
Carboxymethyl starch sodium 80g
Micropowder silica gel 10g
Magnesium stearate 8.5g
The 0.5%PVP alcoholic solution is an amount of
Make 1000
2-hydroxy-4-methyl benzenesulfonic acid was pulverized 100 mesh sieves, and other adjuvant is crossed 80 mesh sieves.With principal agent and microcrystalline Cellulose, lactose, soluble starch, carboxymethyl starch sodium and hydroxypropyl cellulose, cross 60 mesh sieve mix homogeneously.With 0.5%PVP ethanol liquid system soft material, 18 mesh sieves are granulated, and wet grain is in 60 ℃ of oven dry, 16 mesh sieve granulate.Micropowder silica gel, magnesium stearate are crossed 80 mesh sieves, with granule 16 mesh sieve mix homogeneously.Determine that sheet is heavy, tabletting can make 2-hydroxy-4-methyl benzenesulfonic acid vaginal tablet.
Embodiment 6
Get 2 hydroxy-4-methyl benzenesulfonic acid 18g,, add 1.5g sodium lauryl sulphate and 1g poloxamer 188 then, add purified water, be sub-packed in the 50ml Foam bottle, promptly get 2-hydroxy-4-methyl benzenesulfonic acid foam to 200ml with the dissolving of 32g purified water.
Embodiment 7
2-hydroxy-4-methyl benzenesulfonic acid is to the therapeutical effect of cervical erosion rat model
32 of Healthy female rats are divided into normal group, model group, positive controls (Compound Zedoary Turmeric Oil Suppositories 0.02g/kg), experimental group (the 2-hydroxy-4-methyl benzenesulfonic acid gel 0.1048g/kg among the embodiment 2), 8 every group by the body weight stratified random.Get phenol 25g, Radix Acaciae senegalis 35g, glycerol 20ml, adding distil water is made into 25% phenol rubber cement to 100ml.Weigh before the modeling.Each treated animal inserts the about 1cm of vagina place gently with the 1ml vaginal administration device, only injects phenol rubber cement 0.3ml/, every day 1 time, totally 4 times, causes the cervical erosion model, normal group injection isometric(al) excipient (the blank rubber cement that natural gum, glycerol, distilled water are made into).Modeling animal majority occurs that vaginal orifice redness, secretion dense property thing, animal flock together, few moving, a perpendicular hair phenomenon.The 3rd day beginning drug treatment after the modeling, 0.3ml/, normal group and model group give the substrate treatment.Treatment is 12 days continuously.1h weighs after the last administration, uses 3.5% chloral hydrate anesthesia, and eyeball is got blood, measure total white blood cells with cell counter, put to death animal then, get vagina and the uterus subangle place tissue calculating ponderal index of weighing, reuse 10% neutral formalin fixedly vagina and cervix uteri in order to histopathologic examination.
2-hydroxy-4-methyl benzenesulfonic acid is to the influence of cervical erosion rat model cervix uteri inflammation degree
Compare with model group, * represents that significant difference is arranged.
2-hydroxy-4-methyl benzenesulfonic acid is to the influence of total white blood cells in cervical erosion rat model body weight, vagina, cervix uteri ponderal index and the blood
Compare * P＜0.05, * * p＜0.01 with model group; Compare #p＜0.05, ##p＜0.01 with the normal control group
The experimental result of cervical erosion rat model rat therapeutical effect is shown vagina injects that the phenol rubber cement can cause that rat body weight alleviates, vagina and the rising of cervix uteri ponderal index, vagina and cervical tissue hyperemia, edema are remarkable, illustrate that the model manufacturing successfully.After the treatment of 2-hydroxy-4-methyl benzenesulfonic acid gel, the pathology damage of rat model is clearly better, and vagina and cervix uteri ponderal index obviously reduce, and body weight is obviously recovered, and total white blood cells obviously reduces in the blood, compares with model, and significant difference is all arranged.
Embodiment 8
2-hydroxy-4-methyl benzenesulfonic acid is to proteic convergence consolidation
2-hydroxy-4-methyl benzenesulfonic acid is configured to 10 series concentration between the 50%-0.098% according to the gradient concentration dilution method with normal saline, and it is 0.5 geometric ratio series that each concentration is the geometric ratio coefficient.Get some test tubes, add the 2-hydroxy-4-methyl benzenesulfonic acid 0.2ml of 5% Ovum Gallus domesticus album 5ml and each concentration respectively, observe each pipe and have or not albumen precipitation, and the albumen precipitation degree of each pipe relatively.The tannic acid liquid of configuration same train concentration, with the method operation, as positive control, normal saline is as negative control.
2-hydroxy-4-methyl benzenesulfonic acid is to proteic convergence consolidation
| The test tube numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
| Tried thing | 50 | 25 | 12.5 | 6.25 | 3.125 | 1.56 | 0.78 | 0.39 | 0.195 | 0.098 |
| 2-hydroxyl-4-toluene sulfonic acide | +++ | +++ | +++ | +++ | ++ | + | + | ± | - | - |
| Tannic acid | / | / | / | +++ | +++ | +++ | +++ | +++ | ++ | ++ |
| Normal saline | - | - | - | - | - | - | - | - | - | - |
White precipitate is not seen in-expression ,+represent to may be seen indistinctly white precipitate ,+expression has a small amount of white precipitate, ++ expression has more white precipitate, +++expression has a large amount of white precipitates.
The convergence experimental result shows that it is 0.39% that 2-hydroxy-4-methyl benzenesulfonic acid has the threshold concentration of convergence consolidation to albumen, and effect is weaker than the tannic acid with concentration.
Embodiment 9
The vitro antibacterial activity of 2-hydroxy-4-methyl benzenesulfonic acid
MH (DIFCO) broth bouillon pH is transferred to 7.0,15 pounds of sterilizations in 30 minutes, and experimental strain is clinical separation pathogenic bacterium in 2003.
Various test strains are inoculated in the 2ml MH broth bouillon 37 ℃ cultivated 18 hours, be diluted to 10 with MH meat soup
6CFU/ml adopts test tube method as experimental bacteria liquid.2-hydroxy-4-methyl benzenesulfonic acid is made 1% solution with sterile distilled water,, will dilute bacterium liquid 10 again with MH (DIFCO) broth bouillon mixing (streptococcus and enterococcus faecalis add 5% and go the fiber Sanguis caprae seu ovis to make blood training base, and Candida albicans adds 5% glucose)
6CFU/ml adds, and through 37 ℃ of cultivations in 24 hours, observes the result of 2-hydroxy-4-methyl benzenesulfonic acid bacteria growing inhibiting.
The vitro antibacterial activity of 2-hydroxy-4-methyl benzenesulfonic acid
| Test organisms | Gold Portugal bacterium 9776 | Form staph 26069 | Colon bacillus 26 | Enterococcus faecalis 755 | Group B streptococcus 96 | Candida albicans 2 | Candida albicans 6 | Candida albicans 10 | Candida albicans 12 |
| The result | - | - | - | + | + | - | - | - | - |
-for obvious bacteriostasis is arranged ,+for there not being bacteriostasis
2-hydroxy-4-methyl benzenesulfonic acid is selected Candida albicans and golden Portugal bacterium for use to test as can be seen from the results
9776, form staph
26069, colon bacillus
26The obvious suppression effect is arranged, to enterococcus faecalis
765And group B streptococcus
96There is not bacteriostasis.
Embodiment 10
The 400g metacresol is joined in the 1L reaction bulb, and temperature drips 98% sulphuric acid 370.20g at 25-30 ℃ in the control.After being warming up to 80-85 ℃ of reaction 8hr, add deionized water 600ml, make mix homogeneously.Naturally after being chilled to room temperature,, remove unreacted metacresol, remove chloroform under reduced pressure, add the 10g activated carbon again, stir sucking filtration after 15 minutes with 100ml * 3 chloroform extractions.Filtrate cold preservation is spent the night.Filter, filter cake reuse 400ml deionized water recrystallization, 50 ℃ of vacuum dryings obtain 2-hydroxy-4-methyl benzenesulfonic acid 205g.
Claims (9)
1.2-the hydroxy-4-methyl benzenesulfonic acid is as the application of unique active component in antibiotic, the protein coagulation of preparation, astringency and hemostasis medicament.
2. the described application of claim 1 is characterized in that, described medicine is prepared from by 2-hydroxy-4-methyl benzenesulfonic acid and the adjuvant that pharmaceutically allows.
3. the described application of claim 1 is characterized in that, described medicine can be made into any pharmaceutically useful dosage form.
4. the described application of claim 1 is characterized in that described medicine can be made into suppository, gel, solution, ointment, vaginal tablet, vagina soft capsule, spray or foam.
5. the described application of claim 1 is characterized in that, described medicine is that the adjuvant that pharmaceutically allows by the 2-hydroxy-4-methyl benzenesulfonic acid of 0.1%-99.9% weight and 0.1%-99.9% weight is prepared from.
6. the described application of claim 1 is characterized in that, described process for preparing medicine comprises 2-hydroxy-4-methyl benzenesulfonic acid and the blended step of adjuvant that pharmaceutically allows.
7. the described application of claim 1, it is characterized in that, described application is the hemostasis that is used for the treatment of in gynecological after pressure ulcer, cervical polyp excision or the cut sections for microscopic examination that cervical erosion, cervicitis, all kinds of vaginal infection, pruritus vulvae, use pessulum causes, condyloma acuminatum and quicken electric coagulation therapy after wound healing.
8. the described application of claim 1, it is characterized in that, described application is the topical therapeutic that is used for skin wound and pathological changes in surgery and department of dermatologry, the antibacterial of skin surface, treatment of fungal infections, operating hemostasis and be used for the treatment of condyloma acuminatum, described antibiotic be the inflammation that in the department of stomatology, is used for the treatment of oral mucosa and gums, oral ulcer and post tonsillectomic hemostasis.
9. the described application of claim 1 is characterized in that, described application is sterilization and the Personal hygiene cleaning that is used for apparatus, household, medicated clothing as disinfectant.
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| CN1480151A (en) * | 2002-09-04 | 2004-03-10 | 黄振华 | Policresulen lotion |
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| CN1480151A (en) * | 2002-09-04 | 2004-03-10 | 黄振华 | Policresulen lotion |
Non-Patent Citations (6)
| Title |
|---|
| 安明等.聚甲酚磺醛溶液中4种有关物质的HPLC测定.药物分析杂志24 5.2004,24(5),535-537. |
| 安明等.聚甲酚磺醛溶液中4种有关物质的HPLC测定.药物分析杂志24 5.2004,24(5),535-537. * |
| 杨永钢等.反相高效液相色谱法测定聚甲酚磺醛溶液中三组分含量.解放军药学学报19 4.2003,19(4),277-279. |
| 杨永钢等.反相高效液相色谱法测定聚甲酚磺醛溶液中三组分含量.解放军药学学报19 4.2003,19(4),277-279. * |
| 谢荣春等.2,2＇-二羟基-5,5＇-甲叉二-（对甲苯磺酸）及其同分异构物的合成研究.浙江农业大学学报24 3.1998,24(3),摘要. |
| 谢荣春等.2,2＇-二羟基-5,5＇-甲叉二-(对甲苯磺酸)及其同分异构物的合成研究.浙江农业大学学报24 3.1998,24(3),摘要. * |
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